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An agent-based approach for modelling and simulation of glycoprotein VI receptor diffusion, localisation and dimerisation in platelet lipid rafts

Receptor diffusion plays an essential role in cellular signalling via the plasma membrane microenvironment and receptor interactions, but the regulation is not well understood. To aid in understanding of the key determinants of receptor diffusion and signalling, we developed agent-based models (ABMs...

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Autores principales: Tantiwong, Chukiat, Dunster, Joanne L., Cavill, Rachel, Tomlinson, Michael G., Wierling, Christoph, Heemskerk, Johan W. M., Gibbins, Jonathan M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9994409/
https://www.ncbi.nlm.nih.gov/pubmed/36890261
http://dx.doi.org/10.1038/s41598-023-30884-6
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author Tantiwong, Chukiat
Dunster, Joanne L.
Cavill, Rachel
Tomlinson, Michael G.
Wierling, Christoph
Heemskerk, Johan W. M.
Gibbins, Jonathan M.
author_facet Tantiwong, Chukiat
Dunster, Joanne L.
Cavill, Rachel
Tomlinson, Michael G.
Wierling, Christoph
Heemskerk, Johan W. M.
Gibbins, Jonathan M.
author_sort Tantiwong, Chukiat
collection PubMed
description Receptor diffusion plays an essential role in cellular signalling via the plasma membrane microenvironment and receptor interactions, but the regulation is not well understood. To aid in understanding of the key determinants of receptor diffusion and signalling, we developed agent-based models (ABMs) to explore the extent of dimerisation of the platelet- and megakaryocyte-specific receptor for collagen glycoprotein VI (GPVI). This approach assessed the importance of glycolipid enriched raft-like domains within the plasma membrane that lower receptor diffusivity. Our model simulations demonstrated that GPVI dimers preferentially concentrate in confined domains and, if diffusivity within domains is decreased relative to outside of domains, dimerisation rates are increased. While an increased amount of confined domains resulted in further dimerisation, merging of domains, which may occur upon membrane rearrangements, was without effect. Modelling of the proportion of the cell membrane which constitutes lipid rafts indicated that dimerisation levels could not be explained by these alone. Crowding of receptors by other membrane proteins was also an important determinant of GPVI dimerisation. Together, these results demonstrate the value of ABM approaches in exploring the interactions on a cell surface, guiding the experimentation for new therapeutic avenues.
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spelling pubmed-99944092023-03-09 An agent-based approach for modelling and simulation of glycoprotein VI receptor diffusion, localisation and dimerisation in platelet lipid rafts Tantiwong, Chukiat Dunster, Joanne L. Cavill, Rachel Tomlinson, Michael G. Wierling, Christoph Heemskerk, Johan W. M. Gibbins, Jonathan M. Sci Rep Article Receptor diffusion plays an essential role in cellular signalling via the plasma membrane microenvironment and receptor interactions, but the regulation is not well understood. To aid in understanding of the key determinants of receptor diffusion and signalling, we developed agent-based models (ABMs) to explore the extent of dimerisation of the platelet- and megakaryocyte-specific receptor for collagen glycoprotein VI (GPVI). This approach assessed the importance of glycolipid enriched raft-like domains within the plasma membrane that lower receptor diffusivity. Our model simulations demonstrated that GPVI dimers preferentially concentrate in confined domains and, if diffusivity within domains is decreased relative to outside of domains, dimerisation rates are increased. While an increased amount of confined domains resulted in further dimerisation, merging of domains, which may occur upon membrane rearrangements, was without effect. Modelling of the proportion of the cell membrane which constitutes lipid rafts indicated that dimerisation levels could not be explained by these alone. Crowding of receptors by other membrane proteins was also an important determinant of GPVI dimerisation. Together, these results demonstrate the value of ABM approaches in exploring the interactions on a cell surface, guiding the experimentation for new therapeutic avenues. Nature Publishing Group UK 2023-03-08 /pmc/articles/PMC9994409/ /pubmed/36890261 http://dx.doi.org/10.1038/s41598-023-30884-6 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Tantiwong, Chukiat
Dunster, Joanne L.
Cavill, Rachel
Tomlinson, Michael G.
Wierling, Christoph
Heemskerk, Johan W. M.
Gibbins, Jonathan M.
An agent-based approach for modelling and simulation of glycoprotein VI receptor diffusion, localisation and dimerisation in platelet lipid rafts
title An agent-based approach for modelling and simulation of glycoprotein VI receptor diffusion, localisation and dimerisation in platelet lipid rafts
title_full An agent-based approach for modelling and simulation of glycoprotein VI receptor diffusion, localisation and dimerisation in platelet lipid rafts
title_fullStr An agent-based approach for modelling and simulation of glycoprotein VI receptor diffusion, localisation and dimerisation in platelet lipid rafts
title_full_unstemmed An agent-based approach for modelling and simulation of glycoprotein VI receptor diffusion, localisation and dimerisation in platelet lipid rafts
title_short An agent-based approach for modelling and simulation of glycoprotein VI receptor diffusion, localisation and dimerisation in platelet lipid rafts
title_sort agent-based approach for modelling and simulation of glycoprotein vi receptor diffusion, localisation and dimerisation in platelet lipid rafts
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9994409/
https://www.ncbi.nlm.nih.gov/pubmed/36890261
http://dx.doi.org/10.1038/s41598-023-30884-6
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